Summary of the safety profile The safety data of panobinostat have been assessed from a total of 451 patients with multiple myeloma treated with panobinostat in combination with bortezomib and dexamethasone and from a total of 278 patients treated with panobinostat as a single agent.
The safety data reported below are based on the phase III clinical study (Panorama 1) in 381 patients with multiple myeloma treated with 20 mg panobinostat once a day three times per week, on a 2 weeks on and 1 week off dosing regimen in combination with bortezomib and dexamethasone.
0 months. 7% of patients were exposed to study treatment for ≥48 weeks. The most common non-haematological adverse reactions were diarrhoea, fatigue, nausea and vomiting. Treatment-emergent haematological toxicities included thrombocytopenia, anaemia, neutropenia and lymphopenia.
8% of patients. No patient had an absolute QTcF >500 msec. 4%, respectively. 2% of patients. 3%). 2% of placebo + bortezomib + dexamethasone-treated patients. Tabulated list of adverse drug reactions from clinical studies Adverse drug reactions from the phase III study (Panorama 1) are shown in Table 7.
Adverse drug reactions are listed according to system organ classes in MedDRA. Within each system organ class, the adverse drug reactions are ranked by frequency, with the most frequent reactions first. Within each frequency grouping, adverse drug reactions are presented in order of decreasing seriousness.
In addition, the corresponding frequency category for each adverse drug reaction is based on the following convention (CIOMS III): very common (≥1/10); common (≥1/100 to <1/10); uncommon (≥1/1,000 to <1/100); rare (≥1/10,000 to <1/1,000); very rare (<1/10,000); and not known (cannot be estimated from available data).
Table 7 includes adverse drug reactions that occur due to the addition of panobinostat to the bortezomib and dexamethasone combination. e. panobinostat + bortezomib + dexamethasone. For adverse drug reactions that are related to bortezomib or dexamethasone treatment, please refer to the relevant SmPC.
Table 7 Panobinostat adverse drug reactions observed in multiple myeloma patients in the phase III study System Organ Class Frequency Adverse reaction Very common Upper respiratory tract infection, pneumonia Common Septic shock, urinary tract infection, viral infection, oral herpes, Clostridium difficile colitis, otitis media, cellulitis, sepsis, gastroenteritis, lower respiratory tract infection, candidiasis Infections and infestations Uncommon Pneumonia fungal, hepatitis B, aspergillosis Blood and lymphatic system disorders a Very common Pancytopenia, thrombocytopenia, anaemia, leukopenia, neutropenia, lymphopenia Endocrine disorders Common Hypothyroidism Very common Decreased appetite, hypophosphataemia a, hyponatraemia a, hypokalaemia a Metabolism and nutrition disorders Common Hyperglycaemia, dehydration, hypoalbuminaemia, fluid retention, hyperuricaemia, hypocalcaemia, hypomagnesaemia Psychiatric disorders Very common Insomnia Very common Dizziness, headacheNervous system disorders Common Haemorrhage intracranial, syncope, tremor, dysgeusia Eye disorders Common Conjunctival haemorrhage Common Bradycardia, atrial fibrillation, sinus tachycardia, tachycardia, palpitation Cardiac disorders Uncommon Myocardial infarction Very common Hypotension Common Hypertension, haematoma, orthostatic hypotension Vascular disorders Uncommon Shock haemorrhagic Very common Cough, dyspnoea Common Respiratory failure, rales, wheezing, epistaxis Respiratory, thoracic and mediastinal disorders Uncommon Pulmonary haemorrhage, haemoptysis Very common Diarrhoea, nausea, vomiting, abdominal pain, dyspepsia Common Gastrointestinal haemorrhage, haematochezia, gastritis, cheilitis, abdominal distension, dry mouth, flatulence Gastrointestinal disorders Uncommon Colitis, haematemesis, gastrointestinal pain Hepatobiliary disorders Common Hepatic function abnormal, hyperbilirubinaemia a Common Skin lesions, rash, erythemaSkin and subcutaneous disorders Uncommon Petechiae Musculoskeletal and connective tissue disorders Common Joint swelling Renal and urinary disorders Common Renal failure, haematuria, urinary incontinence Very common Fatigue, oedema peripheral, pyrexia, asthenia General disorders and administration site conditions Common Chills, malaise Very common Weight decreasedInvestigations Common Blood urea increased, glomerular filtration rate decreased, blood alkaline phosphatase increased, electrocardiogram QT prolonged, blood creatinine increased a, SGPT alanine transaminase (ALT) increased a, SGOT aspartate transaminase (AST) increased a a Frequency is based on laboratory values Description of selected adverse drug reactions Gastrointestinal Gastrointestinal toxicity, primarily diarrhoea, nausea and vomiting, is among the most frequently reported adverse reactions.
5% […]